Amyloidosis : Introduction , Pathogenesis, Clinical Features

Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing.

Amyloidosis is a systemic disorder that is classified into several types based on the precursor protein. The different types of amyloidosis are classified as systemic or localized. AL (immunoglobulin light chain, historically known as primary) amyloidosis is the most common type of systemic amyloidosis. AL amyloidosis results from an abnormality (dyscrasia) of a type of white blood cell called plasma cells in the bone marrow and is closely related to multiple myeloma. AA (historically known at secondary) amyloidosis is derived from the inflammatory protein serum amyloid A.

AA amyloidosis occurs in association with chronic inflammatory diseases such as the rheumatic diseases, familial Mediterranean fever, chronic inflammatory bowel disease, tuberculosis or empyema. Hereditary amyloidosis is a rare type of amyloidosis that is caused by an abnormal gene. There are several abnormal genes that can cause hereditary amyloidosis, but the most common type of hereditary amyloidosis is called ATTR and caused by changes (pathogenic variants or mutations) in the transthyretin (TTR) gene. Age related amyloidosis, in which the amyloid is derived from wild-type (normal) transthyretin, is a slowly progressive disease that affects the hearts of elderly individuals, usually men and less commonly women, and is called ATTRwt amyloidosis.

Amyloid deposits may occasionally occur in isolation without evidence of a systemic disease; isolated bladder or tracheal amyloidosis are the most common such presentations. Dialysis-related beta2-microglobulin amyloidosis is a type of systemic amyloidosis that can occur in individuals who have experienced long-term kidney dialysis to remove accumulated impurities or wastes in the blood by mechanical filtration.

This form of amyloidosis, also known as AB2MG (amyloid associated with the beta-2m protein), is associated with the aggregation of beta2-microglobulin, a type of amyloid protein that is cleared by the normally functioning kidney. Dialysis-related beta2-microglobulin amyloidosis occurs in patients with near end-stage renal disease. It does not affect individuals with normal or mildly reduced renal function or patients with a functioning renal transplant.